Abstract 9: A Novel Large Cerebral Aneurysm Model in Rats with Intraperitoneal Administration of Beta-AminoPropioNitril-Fumarate

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Abstract

Introduction: Mechanisms of formation, enlargement, and rupture of cerebral aneurysm (CA) are not fully understood. Unveiling the mechanisms lead to the prevention of a life-threatening subarachnoid hemorrhage. Although several CA models in rats have been reported, most of CAs in the models are immature and insufficient for the close investigation into the mechanisms of enlargement and rupture. The establishment of a large CA model is required for full disclosure of the mechanisms.

Methods: A new CA model in rats was designed by modifying the Hashimoto model in that high-dose β-aminopropionitril fumarate (BAPN-F) was administrated intraperitoneally. Seven-week-old male Sprague-Dawley rats were deeply anesthetized, the left common carotid artery was dissected and the bilateral posterior branches of the renal artery were ligated. After the operation, rats were fed food with 8% sodium chloride and divided into 4 groups according to the weekly dose amount of BAPN-F as well as the breeding periods (group 1: n=31, 400mg/kg for 4weeks, group 2: n=31, 400mg/kg for 8weeks, group 3: n=27, 2800mg/kg for 8weeks, group 4: n=13, 2800mg/kg for 12weeks). We then investigated aneurysmal development pathologically along with calculating CA induction rate and mortality rate in each group.

Results: Continuous hypertension were induced in all groups. CA induction rate was 19.4%, 29%, 85.2%, and 84.6% while mortality was 12.9%, 16.1%, 7.4% and 30.1% in the group 1, 2, 3, and 4, respectively. Group 3 has statistically significant differences in both the induction rate (p=0.018) and mortality (p=0.027). Among 4 groups, CAs were located at anterior cerebral artery - ophthalmic artery bifurcation, anterior communicating artery (Acom A), and posterior communication artery (Pcom A). We defined the large CA as over one and a half times the size of its parent artery. Large CAs were predominantly detected at Acom A and Pcom A in the group 3 (22.2%) and 4 (23.1%). In addition, all large CAs were morphologically and histologically similar to that of human.

Conclusions: Intraperitoneal administration of 2800mg/kg BAPN-F enabled us to induce large CAs with 20% induction rate and low mortality. A further investigation of this model should be promising for full disclosure of the CAs mechanisms.

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